Rational prescribing of extended-spectrum penicillin beta-lactamase inhibitor combinations: focus on ticarcillin/clavulanic acid.
OBJECTIVE
To provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles.


METHODS
Published ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid.


RESULTS
Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination.


CONCLUSIONS
Integration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.
Reed
M D
MD
Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
D000367:Age Factors; D002969:Clavulanic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D011307:Drug Prescriptions; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013982:Ticarcillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin